CureGene Pharmaceuticals has announced what it calls ‘groundbreaking preclinical data’ for CG-0416, a novel oral non-GLP-1 weight-loss agent.
It made the announcement in the late-breaking poster session at Obesity Week 2025.
CG-0416 is a liver-targeting thyroid hormone receptor beta (THR-β) agonist. Its highlighted profile—oral administration, potent fat reduction, and muscle preservation, and without GLP-1 target associated side effects—positions it as a potential new paradigm that could advance global obesity treatment beyond current GLP-1-based therapies.
While GLP-1 receptor agonists like semaglutide have demonstrated significant efficacy, they are associated with core challenges including muscle loss, gastrointestinal (GI) side effects, and the inconvenience of injectable administration. CG-0416 has been designed to address these limitations through a distinct mechanism. It precisely activates the THR-β receptor in the liver, directly boosting hepatic metabolism to promote fat burning and energy expenditure, without acting on the central appetite control system. This peripheral mechanism fundamentally avoids the potential psychiatric affects and GI adverse events associated with potent appetite suppression and effectively protects muscle tissue.
Data presented revealed that in diet-induced obese (DIO) mouse models, CG-0416 monotherapy demonstrated superior “high-quality weight loss.” While achieving weight reduction comparable to semaglutide, approximately 95% of the weight loss with CG-0416 came from fat mass reduction, with minimal muscle loss. In contrast, about one-third of semaglutide-induced weight loss was attributed to lean mass reduction. By not strongly suppressing appetite, CG-0416 is expected to significantly reduce nausea, vomiting, and other GI adverse events, potentially leading to better patient adherence. CG-0416 significantly reduced blood and liver lipid levels and improved glucose tolerance.
The studies further explored combination therapies of CG-0416 with various GLP-1 RAs, including semaglutide and oral orforglipron, revealing powerful “1+1>2” synergistic effects.
Combination with semaglutide: The combination increased weight loss from 24% (semaglutide monotherapy) to 40%, with some obese mice returning to a healthy weight range. It also significantly mitigated the muscle loss associated with GLP-1 RA monotherapy, increasing body muscle percentage. Combination with orforglipron: Similar synergistic effects were observed, confirming the robustness of this approach.
The dual-pathway strategy, combining “central appetite regulation (GLP-1 RA) + peripheral liver metabolism activation (CG-0416)”, offers a novel solution for patients requiring profound weight loss and metabolic restoration.
As a once-daily oral agent, CG-0416 greatly enhances convenience and patient compliance. Its advantages cover the needs from different patient populations.
The company said CG-0416 monotherapy is ideal for individuals seeking healthy status (fat loss and muscle preservation) and for patients intolerant to GLP-1-based therapies, while CG-0416 and GLP-1 RA combination provides a more potent, higher-quality (with reduced muscle loss), and sustainable treatment option for patients with obesity and metabolic syndrome.
The data presented firmly establish the strong potential of CG-0416 as a “next-generation benchmark weight-loss therapy” and further validate the efficiency of CureGene’s “Jade” prodrug technology platform. The company said CG-0416 represents not just a supplement to existing treatments, but a critical step toward a future of high-quality, sustainable, and personalised weight management.
Jim Cornall is editor of Deeptech Digest and publisher at Ayr Coastal Media. He is an award-winning writer, editor, photographer, broadcaster, designer and author. Contact Jim here.
